It has been known that diseased/injured microenvironments release different biological cues and follow abnormal regulatory cycles, when compared to physiologically normal cells and tissues. Such dynamic microenvironmental conditions require scientists to develop more effective nanomaterial-based drug delivery systems (DDSs) having the following attributes: i) they can deliver multiple drugs such as organic small molecules, proteins, peptides, DNA, and RNAi molecules without any physicochemical alterations to drug structure, ii) they can modulate the drug-release profile in response to external or internal stimuli for enhancing therapeutic efficacy and minimizing side-effects of drug treatment, and iii) they can monitor the drug release in real time for investigating accumulation of the drugs at the targeted area.
In this regard, mesoporous silica nanoparticles (MSNs) have excellent potential as DDSs owing to their unique porous structure, tunable pore size, biocompatibility, ease of surface functionalization, and overall versatility. The hexagonal-ordered pore network within these MSNs allows for entrapping drugs within these pores by simple diffusion. Additionally, the pores can be functionalized with molecular valves designed to trigger the release of the entrapped drugs in the presence of external or internal stimuli including light, temperature, pH, and biomolecules. While there have been numerous reports on the design and development of stimuli-responsive MSNs for drug delivery, development of strategies for real-time monitoring of drug release inside the targeted cells is still in its nascent stage.
The most widely used amongst these strategies include using fluorescent dyes/drugs as a model cargo system, or conjugating the drugs with caged dyes. However, such strategies come with their own limitations such as difficulty in correlating the release of the fluorescent model dye to that of the actual drug molecules; restricting the usage of fluorescent drugs like doxorubicin as model cargoes, although most of the current drug candidates are non-fluorescent; and possibility of affecting the therapeutic efficacy of the drug owing to structural changes required for conjugation of dyes. Such challenges in investigating the release of drug in complex cellular microenvironments necessitate the development and integration of a real-time monitoring system within the stimuli-responsive nanomaterial-based DDSs.